The purpose of the proposed studies is to examine the role of somatomedin in certain aspects of skeletal development and pathology. One specific aim of these studies is to test the controversial hypothesis that the action of growth hormone (GH) on skeletal growth is mediated by somatomedin-C/Insulin-Like Growth Factor I (Sm-C/IGF-I). The cells responsible for skeletal growth are the chondrocytes of the epiphyseal growth plate. Newly developed molecular biological techniques coupled with culture, RIA, immunoinhibition, and histological techniques will be used to investigate the relationships between GH and somatomedin on growth plate chondrocytes in vitro and in vivo. A further aim is to examine the role of somatomedin in growth plate development. The growth plate is a developmental unit containing cells at various stages of maturation. The relationship between somatomedin and cellular development in the growth plate will be examined using molecular biological, immunocytochemical and culture techniques. Expanding upon these studies, an additional objective of this proposal is to explore the possibility that Sm-C/IGF-I and fibroblast growth factor play a combine role in regulating growth. This work will employ radioligand binding and cell culture techniques to investigate Sm-C/IGF-I and FGF interactions with growth plate chondrocytes in vitro. The long term objective of these studies is to help achieve a basic understanding of the mechanisms of skeletal growth and development. Only with such understanding can needed improvements in existing therapy eventually be achieved.